Effect of angiontensin-(1-7) on development of monocrotaline induced pulmonary arterial hypertension and vascular remodeling

AIM: To investigate the effect of angiotensin-(1-7) [Ang-(1-7)] on the development of monocrotaline(MCT) induced pulmonary arterial hypertension and vascular remodeling.METHODS: 60 Sprgue-Dawely rats were randomly assigned into three groups: control group,PAH group and PAH+Ang-(1-7) group.Rats in PAH group and PAH +Ang-(1-7) group received 60 mg/kg MCT injection subcutaneously and after 24 h received either saline or 24 μg·kg-1·h-1 of Ang-(1-7) injection via osmotic minipumps for 4 weeks.These rats in control group were firstly injected saline subcutaneously and then received saline injection via osmotic minipumps.RESULTS: After 4 weeks,in PAH group,right ventricular systolic pressure(RVSP),right ventricular hypertrophy index(RVHI),percentage of wall thickness(WT%) and percentage of wall area(WA%) of pulmonary artery were significantly increased and NO concentration,the level of endothelial nitric oxide synthase(eNOS),eNOS Ser1177-phosphorylation were significantly decreased compared with control group.However,RVSP,RVHI,WT %,WA % were dramatically decreased in PAH +Ang-(1-7) group and NO concentration,the level of eNOS protein,eNOS Ser1177-phosphorylation were significantly increased compared with PAH group.CONCLUSION: These results suggest that Ang-(1-7) could prevent the development of monocrotaline induced pulmonary arterial hypertension and vascular remodeling,which appears to be associated with up-regulation of NO concentration and the level of eNOS protein,eNOS Ser1177-phosphorylation.